Mechanisms of coronary sinus reducer for treatment of myocardial ischemia: in silico study.

The coronary sinus reducer (CSR) is an emerging medical device for treating patients with refractory angina, often associated with myocardial ischemia. Patients implanted with CSR have shown positive outcomes, but the underlying mechanisms are unclear. This study sought to understand the mechanisms of CSR by investigating its effects on coronary microcirculation hemodynamics that may help explain the therapy's efficacy. We applied a validated computer model of the coronary microcirculation to investigate how CSR affects hemodynamics under different degrees of coronary artery stenosis. With moderate coronary stenosis, an increase in capillary transit time (CTT) [up to 69% with near-complete coronary sinus (CS) occlusion] is the key change associated with CSR. Because capillaries in the microcirculation can still receive oxygenated blood from the upstream artery with moderate stenosis, the increase in CTT allows more time for the exchange of gases and nutrients, aiding tissue oxygenation. With severe coronary stenosis; however, the redistribution of blood draining from the nonischemic region to the ischemic region (up to 96% with near-complete CS occlusion) and the reduction in capillary flow heterogeneity are the key changes associated with CSR. Because blood draining from the nonischemic region is not completely devoid of O2, the redistribution of blood to the capillaries in the ischemic region by CSR is beneficial especially when little or no oxygenated blood reaches these capillaries. This simulation study provides insights into the mechanisms of CSR in improving clinical symptoms. The mechanisms differ with the severity of the upstream stenosis.NEW & NOTEWORTHY Emerging coronary venous retroperfusion treatments, particularly coronary sinus reducer (CSR) for refractory angina linked to myocardial ischemia, show promise; however, their mechanisms of action are not well understood. We find that CSR's effectiveness varies with the severity of coronary stenosis. In moderate stenosis, CSR improves tissue oxygenation by increasing capillary transit time, whereas in severe stenosis, it redistributes blood from nonischemic to ischemic regions and reduces capillary flow heterogeneity.

Effectiveness of Coronary Sinus Reducer for Treatment of Refractory Angina: A Meta-analysis.

BACKGROUND: Refractory angina is a debilitating condition that affects the quality of life of patients worldwide, who after exhausting standard available therapies are regarded as "no option" patients. Recently, CS (coronary sinus) reducer (Neovasc Reducer) implantation became available and is gaining popularity in the treatment of refractory angina. The effectiveness of this therapy was demonstrated in 1 randomised sham-control trial and numerous uncontrolled prospective studies entailing several hundred patients altogether. We performed a meta-analysis to incorporate the data and elucidate its efficacy and safety. METHODS: A meta-analysis of prospective studies assessing the effects of CS narrowing published in English to June 2021 was performed. The primary outcome was the proportion of patients improving ≥ 1 class in the Canadian Cardiovascular Society (CCS) angina score. Other end points included proportion of patients improving ≥ 2 CCS classes, procedural success, periprocedural complications, changes in Seattle Angina Questionnaire (SAQ) scores, and 6-minute walk test (6MWT). RESULTS: Data from 9 studies including 846 patients were included. An improvement of ≥ 1 CCS class occurred in 76% (95% confidence interval [CI] 73%-80%) of patients. Improvement of ≥ 2 CCS classes was observed in 40% of patients (95% CI 35%-46%). Procedure success was 98%, with no major and 3% nonmajor periprocedural complications. Post procedural SAQ scores and 6MWT distance were significantly improved. CONCLUSIONS: In patients suffering from angina refractory to medical and interventional therapies, Reducer implantation improves symptoms and quality of life with a low complication rate. These results are consistent in 1 randomised trial and multiple prospective uncontrolled studies.

High density mapping guided partial antral ablation for a pulmonary vein isolation.

The muscular discontinuities at the pulmonary vein (PV)-left atrial (LA) junction are known. The high-density mapping may help to find the muscular discontinuity. This study evaluated the efficacy of a partial antral ablation for a pulmonary vein (PV) isolation using high density (HD) mapping. A total of 60 drug-refractory atrial fibrillation (AF) patients undergoing catheter ablation were enrolled. The detailed activation mapping of each PV and LA junction was performed using an HD mapping system, and each PV segment's activation pattern was classified into a "directly-activated from the LA" or "passively-activated from an adjacent PV segment" pattern. The antral ablations were performed at the directly-activated PV segments only when the PV had "passively-activated segments". If the PV did not contain passively-activated segments, a circumferential antral ablation was performed on those PVs. A "successful partial antral ablation" was designated if the electrical isolation of targeted PV was achieved by ablation at the directly-activated segments only. If the isolation was not achieved even though all directly-activated segments were ablated, a "failed partial antral ablation" was designated, and then a circumferential ablation was performed. Among 240 PVs, passively-activated segments were observed in 140 (58.3%) PVs. Both inferior PVs had more passively-activated segments than superior PVs, and the posteroinferior segments had the highest proportion of passive activation. The overall rate of successful partial antral ablation was 85%. The atrial tachyarrhythmia recurrence was observed in 10 patients (16.7%) at 1-year. HD mapping allowed the evaluation of the detailed activation patterns of the PVs, and passively-activated segments may represent muscular discontinuity. Partial antral ablation of directly-activated antral segments only was feasible and effective for a PVI.

Feature tracking and mapping analysis of myocardial response to improved perfusion reserve in patients with refractory angina treated by coronary sinus Reducer implantation: a CMR study.

Coronary sinus (CS) Reducer implantation improves myocardial perfusion and symptoms in patients with debilitating refractory angina. Its impact on myocardial remodeling remain uncertain. Aim of the present study was to assess possible impact of CS Reducer on myocardial systolic-diastolic deformation and microstructural remodeling, as assessed through cardiac magnetic resonance (CMR) feature tracking and mapping analysis. Twenty-eight consecutive patients with refractory angina underwent multiparametric stress CMR before and 4 months after CS Reducer implantation. Eight patients were excluded (6 for absence of inducible ischemia, 2 for artifacts). Modifications in 3D systo-diastolic myocardial deformation were evaluated using feature tracking analysis on rest cine images. Myocardial microstructural remodeling was assessed by native T1 mapping, cellular and matrix volume and extracellular volume fraction (ECV). Collaterally, the percentage of ischemic myocardium (ischemic burden %) and the myocardial perfusion reserve index (MPRI) were measured. After CS Reducer implantation, myocardial contractility improved (ejection fraction rose from 61 to 67%; p = 0.0079), along with longitudinal (from - 16 to - 19%; p = 0.0192) and circumferential strain (from - 18 to - 21%; p = 0.0017). Peak diastolic radial, circumferential and longitudinal strain rate did not change (p > 0.05), and no changes in native T1, ECV, cellular and matrix volume were observed. Myocardial perfusion improved, with a reduction of ischemic burden (13-11%; p = 0.0135), and recovery of intramural perfusion balance in segments with baseline ischemia (MPRi endocardial/epicardial ratio from 0.67 to 0.96; p = 0.0107). CS Reducer improves myocardial longitudinal and circumferential strain, without microstructural remodeling and no impact on diastolic proprieties.

Sinus arrest: A rare observation during radiofrequency ablation along the coronary sinus roof.

Catheter-based radiofrequency (RF) ablation targeting segments of the cardiac conduction system and/or selected regions of myocardium is an accepted treatment for many cardiac arrhythmias. On the other hand, while purposeful extension of RF ablation to include nearby cardiac neural elements, particularly epicardial ganglionated plexi (GP), remains a subject of ongoing study, inadvertent stimulation of such structures may occur during an otherwise conventional RF ablation procedure. Thus, asystolic pauses have been observed during RF ablation of left ventricular free-wall accessory pathways, slow AV node pathways, and the left superior pulmonary vein. In this report, sinus arrest occurred within 3.3 s of RF application (40 W at 50°C) along the coronary sinus roof for treatment of an atypical "slow-slow" atrioventricular nodal reentrant tachycardia. Energy delivery was immediately terminated, but asystole persisted for 4.7 s followed by sinus bradycardia. The procedure was temporarily halted, but later was successfully resumed. Given the latency from terminating RF to return of sinus node function, the sinus arrest was likely a centrally mediated reflex vagal response. Consequently, while parasympathetic ganglia near the CS os are believed to principally innervate the AV node, not the sinus node, our observation highlights the neural cross-communications that likely exist in this region of the heart.

Incremental prognostic value of coronary flow reserve determined by phase-contrast cine cardiovascular magnetic resonance of the coronary sinus in patients with diabetes mellitus.

BACKGROUND: Although non-invasive assessment of coronary flow reserve (CFR) by cardiovascular magnetic resonance (CMR) provides prognostic information for patients with diabetes mellitus (DM), the incremental prognostic value of CMR-derived CFR remains unclear. PURPOSE: To evaluate the incremental prognostic value of CMR-derived CFR for patients with DM who underwent stress CMR imaging. MATERIALS AND METHODS: A total of 309 patients with type 2 DM [69 ± 9 years; 244 (78%) male] assessed between 2009 and 2019 were retrospectively reviewed. Coronary sinus blood flow (CSBF) was measured using phase contrast (PC) cine CMR. CFR was calculated as the CSBF during adenosine triphosphate infusion divided by that at rest. Major adverse cardiac events (MACE) were defined as death, acute coronary syndrome, hospitalization due to heart failure exacerbation, or sustained ventricular tachycardia. The incremental prognostic value of CFR over clinical and CMR variables was assessed by calculating the C-index and net reclassification improvement (NRI). RESULTS: During a median follow-up of 3.8 years, 42 patients (14%) experienced MACE. The annualized event rate was significantly higher among patients with CFR < 2.0, regardless of the presence of late gadolinium enhancement (LGE) (1.4% vs. 9.8%, p = 0.011 in the LGE (-) group; 1.8% vs. 16.9%, p < 0.001 in the LGE (+) group). In addition, this trend was maintained in the subgroups stratified by presence or absence of ischemia (0.3% vs. 6.7%, p = 0.007 in the ischemia (-) group; 3.9% vs. 17.1%, p = 0.001 in the ischemia (+) group). Adding CFR to the risk model (age + gender + left ventricular ejection fraction + %LGE + %ischemia) resulted in a significant increase of the C-index from 0.838 to 0.870 (p = 0.038) and an NRI of 0.201 (0.004-0.368, p = 0.012). CONCLUSION: PC cine CMR-derived CFR of the coronary sinus may be useful as a prognostic marker for DM patients, incremental to common clinical and CMR parameters. Due to the high prevalence of coronary microvascular dysfunction, the addition of CFR to conventional vasodilator stress CMR imaging may improve risk stratification for patients with DM.

Ablation of atrioventricular-nodal-reentrant- tachycardia in a patient with left-sided superior vena cava and dilated coronary sinus.

Atrioventricular (AV)-nodal-reentrant-tachycardia is a rare association in a patient with persistent left-sided superior vena cava and dilated coronary sinus. There are a few inherent difficulties in ablation in this condition, viz., difficulty in localization of good site for ablation and difficulty in stabilization of the ablation catheter at the designated site, making it difficult to produce transmural lesions and increasing risk of producing AV block. We hereby present a case highlighting the difficulties and possible solutions for them.

Recurrent Atrial Fibrillation with Isolated Pulmonary Veins: What to Do.

When patients have symptomatic recurrent atrial tachyarrhythmias after 2 months following pulmonary vein antral isolation, a repeat ablation should be considered. Patients might present with isolated pulmonary veins posterior wall. In these patients, posterior wall isolation is extended, and non-pulmonary vein triggers are actively sought and ablated. Moreover, in those with non-paroxysmal atrial fibrillation or a known higher prevalence of non-pulmonary vein triggers, empirical isolation of the superior vena cava, coronary sinus, and/or left atrial appendage might be performed. In this review, we will focus on ablation of non-pulmonary vein triggers, summarizing our current approach for their mapping and ablation.

Beyond Pulmonary Vein Isolation in Nonparoxysmal Atrial Fibrillation: Posterior Wall, Vein of Marshall, Coronary Sinus, Superior Vena Cava, and Left Atrial Appendage.

The optimal ablation strategy for non-paroxysmal atrial fibrillation remains controversial. Non-PV triggers have been shown to have a major arrhythmogenic role in these patients. Common sources of non-PV triggers are: posterior wall, left atrial appendage, superior vena cava, coronary sinus, vein of Marshall, interatrial septum, crista terminalis/Eustachian ridge, and mitral and tricuspid valve annuli. These sites are targeted empirically in selected cases or if significant ectopy is noted (with or without a drug challenge), to improve outcomes in patients with non-paroxysmal atrial fibrillation. This article focuses on summarizing the current evidence and the approach to mapping and ablation of these frequent non-PV trigger sites.

The complexity of clinically-normal sinus-rhythm ECGs is decreased in equine athletes with a diagnosis of paroxysmal atrial fibrillation.

Equine athletes have a pattern of exercise which is analogous to human athletes and the cardiovascular risks in both species are similar. Both species have a propensity for atrial fibrillation (AF), which is challenging to detect by ECG analysis when in paroxysmal form. We hypothesised that the proarrhythmic background present between fibrillation episodes in paroxysmal AF (PAF) might be detectable by complexity analysis of apparently normal sinus-rhythm ECGs. In this retrospective study ECG recordings were obtained during routine clinical work from 82 healthy horses and from 10 horses with a diagnosis of PAF. Artefact-free 60-second strips of normal sinus-rhythm ECGs were converted to binary strings using threshold crossing, beat detection and a novel feature detection parsing algorithm. Complexity of the resulting binary strings was calculated using Lempel-Ziv ('76 & '78) and Titchener complexity estimators. Dependence of Lempel-Ziv '76 and Titchener T-complexity on the heart rate in ECG strips obtained at low heart rates (25-60 bpm) and processed by the feature detection method was found to be significantly different in control animals and those diagnosed with PAF. This allows identification of horses with PAF from sinus-rhythm ECGs with high accuracy.

STIM1-Ca2+ signaling in coronary sinus cardiomyocytes contributes to interatrial conduction.

Pacemaker action potentials emerge from the sinoatrial node (SAN) and rapidly propagate through the atria to the AV node via preferential conduction pathways, including one associated with the coronary sinus. However, few distinguishing features of these tracts are known. Identifying specific molecular markers to distinguish among these conduction pathways will have important implications for understanding atrial conduction and atrial arrhythmogenesis. Using a Stim1 reporter mouse, we discovered stromal interaction molecule 1 (STIM1)-expressing coronary sinus cardiomyocytes (CSC)s in a tract from the SAN to the coronary sinus. Our studies here establish that STIM1 is a molecular marker of CSCs and we propose a role for STIM1-CSCs in interatrial conduction. Deletion of Stim1 from the CSCs slowed interatrial conduction and increased susceptibility to atrial arrhythmias. Store-operated Ca2+ currents (Isoc) in response to Ca2+ store depletion were markedly reduced in CSCs and their action potentials showed electrical remodeling. Our studies identify STIM1 as a molecular marker for a coronary sinus interatrial conduction pathway. We propose a role for SOCE in Ca2+ signaling of CSCs and implicate STIM1 in atrial arrhythmogenesis.

Prognostic implication of global myocardial blood flow in patients with ST-segment elevation myocardial infarction.

The prognostic implications of cardiovascular magnetic resonance imaging (CMR)-derived hyperemic myocardial blood flow (MBF) in patients with ST-elevation myocardial infarction (STEMI) are unknown. This study sought to investigate the incremental prognostic value of hyperemic MBF over conventional CMR markers to identify patients with high risk of future incidence of patient-oriented composite outcomes (POCO) and major adverse cardiac events (MACE) after STEMI. A total of 237 patients who presented with STEMI were prospectively enrolled. The CMR protocol included left-ventricular ejection fraction (LVEF), late gadolinium enhancement (LGE) and microvascular obstruction (MVO) measurement, and volumetric MBF assessment. During a median follow-up of 2.6 years, 47 patients experienced POCO (primary outcome) and 21 patients had MACE. In a multivariable model, multivessel disease, LGE, MVO, and hyperemic MBF were independently associated with POCO. Addition of hyperemic MBF to the model consisting of GRACE score, multivessel disease, LVEF, LGE, and MVO significantly improved the predictive efficacy (integrated discrimination improvement 0.020, p = 0.021). Patients with low hyperemic MBF had significantly higher incidence of MACE compared to those with high hyperemic MBF in propensity score matching analysis (p = 0.018). In conclusion, CMR-derived hyperemic MBF could provide independent and incremental prognostic value over LVEF, LGE, and MVO in patients with STEMI.

Simultaneous pacing from two branches of coronary sinus in a patient with prosthetic tricuspid valve and complete heart block.

BACKGROUND: Complete heart blocks underwent to permanent pacemaker placement are a common complication of tricuspid valve replacement (TVR). If indicated, endocardial placement of a right ventricular (RV) lead is precluded in the presence of mechanical TVR. CASE PRESENTATION: A 20-year-old female patient firstly underwent metallic prosthetic valve operation with tricuspid valve endocarditis in 2014. Three years after the operation, echocardiography revealed dysfunction of the prosthetic valve thus reoperation was decided. In the second operation, the patient underwent a bioprosthesis valve and AV complete block developed in the postoperative period. Left ventricular ejection fraction (EF) was 45% was found on echocardiography. Pacemaker dependence of the patient, it was aimed to place two electrodes into the left ventricle. Electrodes were placed the target two branches in coronary sinus (CS) and right atrium. Univentricular bifocal pacing was enabled to work. CONCLUSION: Electrode placement in the CS is a very good alternative to epicardial surgical lead placement in cases where endocardial lead placement from the right atrium to the RV is contraindicated. In patients with lower left ventricular EF who will be pacemaker dependent, the insertion of two electrodes into the CS to prevent pacemaker is a safe and effective treatment.

Implantation of a Coronary Sinus Reducer to Treat Refractory Angina in a 38-Year-Old with an Anomalous Left Coronary Artery and No Revascularization Options.

A 38-year-old female with anomalous left coronary artery from the pulmonary artery presented with refractory angina (Canadian Cardiovascular Society [CCS] class 4). Having failed two previous internal mammary artery grafts to the left anterior descending artery and with no percutaneous revascularization options, she underwent coronary sinus reducer implantation, which improved her symptoms (CCS 0), quality of life, and corresponded to an improvement in ischemia on myocardial perfusion scanning. This case report describes an unusual case of refractory angina in the context of congenital heart disease, illustrates the benefit of this novel hourglass-shaped stent in improving ischemia, quality of life, depression and anxiety, and highlights the importance of managing these patients in multidisciplinary teams.